Project Summary TOC2: High quality and high throughput Small Angle X-ray Scattering A sequence scale structural perspective coupled to an understanding of how these structures change during function is fundamental for mechanistic insights into bio-molecules and can be obtained by combining Small Angle X-ray Scattering (SAXS) with high-resolution snapshots of structure. Furthermore, efficiently identifying the conditions and constructs by SAXS that promote the greatest structural homogeneity in conformation and assembly is hugely advantageous to capture a high- resolution snapshot whether from electron microscopy (EM), macromolecular X-ray crystallography (MX) or nuclear magnetic resonance (NMR). The SIBYLS group has been instrumental in developing a productive SAXS community and advancing powerful SAXS tools for structural biology. Through ALS-ENABLE, TOC2 will provide efficient access to SAXS analyses for hundreds of NIH investigators. By leveraging established technologies developed for high-throughput (HT) assays, SIBYLS is increasing SAXS throughput and decreasing sample size 10-fold. HT-SAXS translates into greater access for more investigators and projects. However, to maximize this transformation at SIBYLS for NIH users, we must develop a supporting infrastructure that establishes an equally efficient pipeline from the time investigators send their samples to the time they receive processed data. We will make use of shared resources and an economy of scale through ALS-ENABLE to support programming of advanced web tools delivering a pipeline that relies heavily on a robust computational infrastructure to organize, process, and store data. These tools and TOC2 activities will be designed to facilitate productive investigator and beamline staff interactions. The advanced technologies we employ will generate abundant data necessitating that all data processing steps must be adapted so that the tremendous developments made by our peers can be effectively applied. In concert, TOC2 will apply automated data analyses so users without SAXS experience can efficiently extract useful information. The significant increase in throughput of HT-SAXS allows time to support users for size-exclusion- chromatography and time-resolved SAXS (SEC-SAXS and TR-SAXS). These existing capabilities are greatly enhanced by our new detector technology. Building on our HT-SAXS framework, TOC2 will vastly increase access to these technologies to meet growing demand. For analysis of HT-SAXS, SEC-SAXS and TR-SAXS data TOC2 will provide our computational tools and those developed by others as web-accessible applications. Through strategic partnership with all components of ALS- ENABLE, and following through on TOC2 Aims, we will make SAXS a natural part of the workflow in any project using synchrotron technologies. We increase the value of SAXS experiments and increase accessibility ? providing quality in quantity.